Delving into the Molecular World of Single Ventricle Congenital Heart Disease

Abstract

Purpose of review: Given a general lack of emphasis on the molecular underpinnings of single ventricle (SV) congenital heart diseases (CHD), our review highlights and summarizes recent advances in uncovering the genetic and molecular mechanisms in SV CHD etiology.

Recent findings: While common SV-associated genetic mutations were found in key cardiac transcription factors, other mutations were sporadic. With advances in genetic sequencing technologies and animal models, more disease-associated factors have been identified to act in critical cardiac signaling pathways such as NOTCH, Wnt, and TGF signaling. Recent studies have also revealed that different cardiac lineages play different roles in disease pathogenesis. SV defects are attributed to complex combinations of genetic mutations, indicating that sophisticated spatiotemporal regulation of gene transcription networks and functional cellular pathways govern disease progression. Future studies will warrant in-depth investigations into better understanding how different genetic factors converge to influence common downstream cellular pathways, resulting in SV abnormalities.

Keywords: Atrioventricular valve hypoplasia; Congenital heart disease; Double inlet left ventricle; Double outlet left ventricle; Hypoplastic left heart syndrome; Septal defects.